This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite the success of highly active antiretroviral therapy (HAART), great concern remains due to rapid emergence of new HIV-1 genetic variants that help the virus escape host immunity and multidrug therapies. Hence, the need to develop new anti-HIV therapeutic drugs and search for new targets remains very high. To this end, we have solved a high-resolution NMR structure for an RNA stem-loop structure, SL1, from the 5'-untranslated region of the HIV-1 RNA genome. This structure has strongly concerved motif, a G-rich internal loop (GRIL), and it is involved in the dimerization of the RNA genome and RNA packaging, two crucial stages of the HIV-1 life cycle. We plan to use the SL1 NMR structure to carry out a computational screening of small molecules, looking for ligands that would interfere with the HIV-1 life cycle.